1. Technical Field
This invention relates to methods and devices for improved ionization, collection, focusing and transmission of ions, generated at or near atmospheric pressure, of gaseous analytes or analytes on surfaces for introduction into a mass spectrometer and other gas-phase ion analyzers and detectors.
2. Description of Related Art
The generation of ions at or near atmospheric pressure is accomplished using a variety of means, including, electrospray (ES), atmospheric pressure chemical ionization (APCI), atmospheric pressure matrix assisted laser desorption ionization (AP-MALDI), discharge ionization, 63Ni sources, inductively coupled plasma ionization, and photoionization. A general characteristic of these atmospheric or near atmospheric ionization sources is the dispersive nature of the ions once produced. Needle sources such as electrospray and APCI disperse ions radially from the axis in the high electric fields emanating from needle tips. Aerosol techniques disperse ions in the radial flow of fluid emanating from tubes and nebulizers. Even desorption techniques such as atmospheric pressure MALDI will disperse ions in a solid angle from a surface. The radial cross-section of many dispersive sources can be as large as 5 or 10 centimeters in diameter.
As a consequence of a wide variety of dispersive processes, efficient sampling of ions from atmospheric pressure sources to small cross-sectional targets or through small cross-sectional apertures and tubes (usually less than 1 mm) into a mass spectrometer (MS) or other sensor capable of detecting and identifying ions becomes quite problematic. This problem becomes amplified if the source of ions is removed from the regions directly adjacent to the aperture. Consequently, there is a tremendous loss of ions prior to entry into the sensor for detection and identification, as shown by the following examples.
The simplest approach to sampling dispersive atmospheric sources is to position the source on axis with a sampling aperture or tube. The sampling efficiency of simple plate apertures is generally less than 1 ion in 104. U.S. Pat. No. 4,209,696 (1980) to Fite discloses an electrospray source with a pinhole aperture, while U.S. Pat. No. 5,965,884 (1999) and World patent 99/63576 (1999) both to Laiko et al. discloses an atmospheric pressure MALDI source configured with a pinhole or aperture in a plate. An atmospheric pressure source disclosed in Japanese patent 04215329 (1994) by Kazuaki et al. is also representative of this approach. In general, these methods are severely restricted by the need for precise aperture alignment and source positioning, and characterized by very poor sampling efficiencies.
U.S. Pat. No. 6,534,765 (2003) and World patent 01/33605 (1999) both to Robb et al. discloses a low field photoionization source developed for liquid chromatography-mass spectrometry (LC/MS) applications. The use of this low field photo-ionization source has lead to some improvement in sampling efficiency from atmospheric pressure sources, but these sources also suffer from a lower concentration of reagent ions when compared to traditional APCI sources.
A wide variety of ion source configurations utilize conical skimmer apertures in order to improve collection efficiency over planar devices. This approach to focusing ions from atmospheric sources is limited by the acceptance angle of the electrostatic fields generated at the cone. Generally, source position relative to the cone is also critical to performance, although somewhat better than planar apertures. Conical apertures are the primary inlet geometry for commercial inductively coupled plasma (ICP/MS) with closely coupled and axially aligned torches. Examples of conical-shaped apertures are prevalent in ES and APCI (U.S. Pat. No. 5,756,994), and ICP (U.S. Pat. No. 4,999,492) inlets. As with planar apertures, source positioning relative to the aperture is critical to performance and collection efficiency is quite low.
Another focusing alternative utilizes a plate lens with a large hole in front of an aperture plate or tube for transferring sample into the vacuum system. The aperture plate is generally held at a high potential difference relative to the plate lens. This approach is referred to as the “Plate-Well” design which is disclosed, with apertures, in U.S. Pat. Nos. 4,531,056 (1985) to Labowsky et al., 5,412,209 (1995) to Covey et al., and 5,747,799 (1998) to Franzen; and with tubes as disclosed in U.S. Pat. Nos. 4,542,293 (1985) to Fenn et al., 5,559,326 (1996) to Goodley et al., and 6,060,705 (2000) to Whitehouse et al.
This configuration creates a potential well that penetrates into the source region and shows a significant improvement in collection efficiency relative to plate or cone apertures. But it has a clear disadvantage in that the potential well resulting from the field penetration is not independent of ion source position, or potential. Furthermore, high voltage needles can diminish this well and off-axis sources can affect the shape and collection efficiency of the well. Optimal positions are highly dependent upon flow (liquid and, concurrent and counter-current gas flows) and voltages. This type of design is reasonably well suited for small volume sources such as nanospray while larger flow sources are less efficient. Because this geometry is generally preferred over plates and cones, it is seen in most types of atmospheric source designs. Several embodiments of atmospheric pressure sources have incorporated grids in order to control the sampling of gas-phase ions. U.S. Pat. No. 5,436,446 (1995) to Jarrell et al. utilized a grid that reflected lower mass ions into a collection cone and passed large particles through the grid. This modulated system was intended to allow grounded needles and collection cones or apertures, while the grid would float at high alternating potentials. This device had limitations with the duty cycle of ion collection in a modulating field (non-continuous sample introduction) and spatial and positioning restrictions relative to the sampling aperture. U.S. Pat. No. 6,207,954 (2001) to Andrien et al. used grids as counter electrodes for multiple corona discharge sources configured in geometries and at potentials to generate ions of opposite charge and monitor their interactions and reactions. This specialized reaction source was not configured with high field ratios across the grids and was not intended for high transmission and collection, rather for generation of very specific reactant ions. An alternative atmospheric pressure device disclosed in Japanese patent 10088798 (1999) to Yoshiaki utilized on-axis hemispherical grids in the second stage of pressure reduction. Although the approach is similar to the present device in concept, it is severely limited by gas discharge that may occur at these low pressures if higher voltages are applied to the electrodes and the fact that most of the ions (>99%) formed at atmospheric pressure are lost at the cone-aperture from the movement from atmospheric pressure into the first pumping stage.
A presentation by Cody et al. entitled “DART™: Direct Analysis in Real Time for Drugs, Explosives, Chemical Agents and More . . . ” made in 2004 (American Society for Mass Spectrometry Sanibel Conference on Mass Spectrometry in Forensic Science and Counter-terrorism, Clearwater, Fla., Jan. 28-Feb. 1, 2004) and U.S. patent publication 2005/0056775 (2005), U.S. Pat. No. 6,949,741 and foreign patent application WO 04/098743 to Cody et al. has disclosed an ionization source and detection technique that incorporates a gas-discharge atmospheric ionization source configured as a tube or gun with a grided aperture or opening at the exit of the tube leading into a low-field reaction region upstream of the sampling aperture of a mass spectrometer for the purpose of ionizing gas-phase molecules through the means of atmospheric pressure ionization.
Grids are also commonly utilized for sampling ions from atmospheric ion sources utilized in ion mobility spectrometry (IMS). Generally, for IMS analysis, ions are pulsed through grids down a drift tube to a detector as shown in U.S. Pat. No. 6,239,428 (2001) to Kunz. Great effort is made to create a planar plug of ions in order to maximize resolution of components in the mobility spectrum. These devices generally are not continuous, nor are they operated such that ions are focused into apertures or capillaries at the atmospheric-vacuum interface of mass analyzers.
The conclusion is that a highly efficient sample or analyte ionization source is needed that allows collection and transmission of most sample ions to the inlet of mass spectrometers, ion mobility spectrometers or other sensors. Such a source, lacking positional dependence is presented herein.